SBRT +/- Pembrolizumab in Patients With Local-Regionally Recurrent or Second Primary Head and Neck Carcinoma

NCT03546582 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: RTOG 3507
• Study Type: interventional
• Target: 86
• Locations: 2 countries
• Sites: 18

Brief Summary

This phase II trial with a safety run-in component will evaluate whether the addition of pembrolizumab to Stereotactic Body Radiation Therapy (SBRT) re-irradiation will improve the progression-free survival for patients with recurrent or new second primary Head and Neck Squamous Cell Carcinoma (HNSCC).

Conditions

Head and Neck Squamous Cell Carcinoma (HNSCC)

Keywords

HNSCC; Head and Neck Squamous Cell Carcinoma; KEYSTROKE

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  The time from randomization to the first documented progressive disease (PD) per RECIST 1.1 or death due to any cause, whichever comes first.

  Assessed up to 5 years

Secondary Outcomes (1)

• Overall Survival (OS)

  Assessed up to 5 years

Study Arms (2)

Arm I

EXPERIMENTAL

Patients receive Stereotactic Body Radiation Therapy (SBRT) over 2 weeks and then receive pembrolizumab every 3 weeks for up to 2 years.

Drug: Pembrolizumab; Radiation: Stereotactic Body Radiation Therapy (SBRT)

Arm II

OTHER

Patients receive Stereotactic Body Radiation Therapy (SBRT) over 2 weeks. Arm II patients who experience progressive disease within 2 years after the start of SBRT will be allowed to cross over to receive pembrolizumab for up to 2 years.

Radiation: Stereotactic Body Radiation Therapy (SBRT)

Interventions

Pembrolizumab DRUG

Anti-PD-1 targeted immunotherapy

Also known as: Keytruda

Arm I

Stereotactic Body Radiation Therapy (SBRT) RADIATION

High-precision radiotherapy

Also known as: SBRT

Arm I; Arm II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically (histologically or cytologically) confirmed diagnosis of locoregional recurrent or any new primary squamous cell carcinoma of the head and neck (including of the nasopharynx or paranasal sinus) that is not amenable to curative resection.
• Patients for whom curative resection would be medically contraindicated and/or would impose excessive surgical risk are eligible.
• Patients who are medically and surgically resectable but for whom surgery would be associated with undue surgical morbidity are eligible.
• For purposes of this protocol, undue surgical morbidity would include total glossectomy; carotid artery resection; laryngectomy or pharyngolaryngectomy; and major ablative resection requiring free flap reconstruction. Patients with primary tumors that can be resected without the forgoing are ineligible.
• The principal investigators are available to review these criteria on a case by case basis if helpful to the enrolling institution.
• A new primary HNSCC is defined where any one of the following criteria are met:
• Metachronous invasive SCC developing ≥ 6 months after an index HNSCC, more than 3 cm from the index lesion;
• SCC developing in the same region as the index SCC if ≥ 36 months after the index diagnosis and if within 3 cm of a site where disease was completely resected or complete response was documented;
• New SCC that is cytologically or molecularly distinct from index SCC (e.g. new HPV negative SCC with prior index SCC that was HPV positive).
• Tumor tissue testing for p16 status is required for base of tongue, soft palate, and tonsil cancer. If a p16 testing has been previously performed on an oropharynx cancer that has recurred, then repeat testing for p16 status is not required. Participants whose first cancer was an unknown primary must have p16 testing from either the new primary tumor or the recurrent cancer.
• Prior radiotherapy (RT) to the head and neck (30 Gy minimum)
• Disease must be limited to a single site or adjacent sites that can be treated in a single contiguous target volume for which the maximum total tumor dimension (GTV) must be \<7.5cm. Examples of eligible patients include:
• A primary site recurrence in the oropharynx with a concurrent level 2 nodal mass, or a laryngeal recurrence with a level 3 nodal mass
• Multiple nodes in the same (level 2) or adjacent nodal levels (levels 2 and 3)
• Skull base recurrence with a lateral pharyngeal or high level 2 node

You may not qualify if:

• Distant metastases.
• Tumors that involve more than 180 degrees of the carotid artery that directly communicates with the skin or mucosal surface (e.g., if the tumor communicates with either external air outside of the skin, or internal air inside mucosal surfaces) on diagnostic CT or MRI of the neck within 56 days prior to entry.
• Note: Tumors that involve \>180 degrees of the carotid, and even those that fully encase the carotid artery are eligible if they do not meet the above criterion. Investigators should email the Study Principal Investigators to review any cases whose eligibility due to carotid encasement are unclear.
• Investigators are encouraged to review the CT simulation imaging and ensure that tumor progression has not occurred whereby patients who were initially eligible based on diagnostic imaging, would be rendered ineligible based on CT simulation imaging (e.g. tumor size \>7.5cm, skin involvement, \>180 degrees of carotid encasement by tumor). If this does occur, the patient should be removed from the study and the Radiation Oncology Co-PIs should be notified via email. Note: It is strongly recommended that CT simulation be performed prior to entry.
• Patients with gross skin involvement (i.e. tumor ulceration through the skin) are excluded. Patients with tumor approaching the skin but in which the overlying skin remains intact are eligible, providing that planning constraints can be achieved without the use of bolus.
• Disease that requires two or more discontiguous target volumes will be ineligible. Examples of such cases include:
• Bilateral nodal targets
• Level 2 and level 4 nodes
• An oropharyngeal recurrence with a low level 4 node;
• Patients for whom the maximal total tumor dimension (GTV) is \>7.5cm
• Prior radiation to primary tumor within 6 months of entry
• Prior systemic therapy, investigational agent or investigational device within 28 days of start of study treatment.
• Surgical resection of the qualifying cancer is not permitted. (Patients who have undergone biopsies are eligible). Patients without radiographically apparent gross tumor are ineligible. For cases where an operation more extensive than a biopsy was performed but radiographically apparent gross residual tumor remains, will be reviewed by the Surgical Co-PI for determination of eligibility.
• No concurrent treatment with other investigational agent or investigational device.
• Prior therapy with a checkpoint inhibitor (eg anti-CTLA-4, anti-PD-1 or anti-PD-L1 therapy).

Sponsors & Collaborators

• RTOG Foundation, Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (18)

University of Arizona Cancer Center - North Campus

Tucson, Arizona, 85719, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Cleveland Clinic - Weston

Weston, Florida, 33331, United States

Location

University of Louisville, James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Washington University St. Louis

St Louis, Missouri, 63110, United States

Location

Northwell Health

Lake Success, New York, 11042, United States

Location

University of Cincinnati Cancer Center - UC Medical Center

Cincinnati, Ohio, 45219, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

University of Pittsburgh Medical Center Shadyside

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Centre Hospitalier de l'université de Montréal

Montreal, Quebec, H2X 3E4, Canada

Location

McGill University

Montreal, Quebec, H4A 3J1, Canada

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab; Radiosurgery

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Stuart J. Wong, MD

  RTOG Foundation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2018
• First Posted: June 6, 2018
• Study Start: November 14, 2018
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2029
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3); US (15)